The Genetic Roots of Disease: Landmark Map Reveals the Genetic Wiring of Cellular Life

University of Toronto

In Brief

A new genetic map has been unveiled showing how genes work in a hierarchy to support life

Researchers are hoping it can shed light on how to better fight disease.

A Genetic GPS of Sorts

While many scientists are busy trying to chart the known universe, a team of researchers from the University of Toronto’s Donnelly Center have charted a different space — the genetic space of a cell. In a research breakthrough, University of Toronto professors Brenda Andrews and Charles Boone, with Chad Myers of the University of Minnesota-Twin Cities, have managed to map the global genetic network of a cell.

The groundbreaking research, published in Science, took 15 years to complete. Studying the genes of yeast cells, the researchers realized that genes in cells work in hierarchical networks to organize cellular life. Yeast cells are excellent stand-ins for human cells because most of its 6,000 genes are also found in humans — and it was relatively easier than studying 20,000 human genes.

The researchers decided that they needed to look beyond just the role and function of one gene in order to understand its effect in the entire system. More than a decade of study revealed that genes actually interact in groups.

A “Reference Guide”

The yeast genetic map showed which genes actually work together in a cell. The notion that genes “buffer” other genes came about 10 years ago and was confirmed by Andrews and Boone. They went through the process of deleting yeast gene pairs, leaving only what is essential for life to survive. As was determined a decade ago, only a small fraction of genes are essential for life (even human life) and yet there are a great number of genes in a being’s genome. Thus, the “buffer” theory.

Credits: Charles Boone

The research was able to identify “synthetic lethal” genes — gene pairs that govern a function, and destroying both pairs kill that particular function. Destroying just one, however, let’s the other pair take over that gene’s role. It is becoming clear that these functional back up genes also exist in human cells.

“We’ve created a reference guide for how to chart genetic interactions in a cell,” Michael Costanzo explains. “We can now tell what kind of properties to look for in searching for highly connected genes in human genetic networks with the potential to impact genetic diseases.” Costazo is one of the researchers who spearheaded the study.

With a similar map of genetic interactions in human cells an inevitable next step, the concept of synthetic lethality will even be more useful in fighting diseased cells — such as cancer. “We have tested the method to completion in a model system to provide the proof of principle for how to approach this problem in human cells. There’s no doubt it will work and generate a wealth of new information,” says Boone.

If scientists can find the buffer or back-up gene of mutated cells, it would be easier to target just these with specific drugs and leave the healthy ones intact.